Histochemistry and Cell Biology最新文献

{"title":"Quercetin enhances the renoprotective effects of phosphodiesterase inhibitors by attenuating endoplasmic reticulum stress-induced cellular apoptosis via modulation of GRP75/CHOP/Bax/Bcl2 pathway.","authors":"Gehad Nasr, Doaa Mohamed Elroby Ali, Michael A Fawzy, Fares E M Ali, Moustafa Fathy","doi":"10.1007/s00418-026-02534-1","DOIUrl":"10.1007/s00418-026-02534-1","url":null,"abstract":"<p><p>This study investigated the ability of quercetin (QU) alone or with sildenafil (Sild) or pentoxifylline (PTX) to modulate carbon tetrachloride (CCl₄)-induced renal fibrosis in Wistar albino rats. Renal fibrosis was induced by intraperitoneal injection of CCl₄ (1.5 ml/kg, three times weekly for 10 weeks). Rats received oral doses of QU (50 mg/kg once daily), PTX (50 mg/kg once daily), and Sild (10 mg/kg twice daily) separately or in combination from week 7 to week 10. CCl₄ induced severe renal injury as indicated by urinary electrolytes disturbance, renal function impairment, increased oxidative stress, inflammation, up-regulation of endoplasmic reticulum (ER) stress markers (CHOP, GRP75), and apoptosis (Bax), as well as down-regulation of defense proteins (Bcl2, Nrf2, HO-1). QU, Sild, and PTX, alone or in combination, improved renal function and alleviated histological changes. The combination of QU with Sild or PTX resulted in greater renoprotection by regulating several key pathways, including reductions in ER stress, enhanced antioxidative defenses, and regulation of apoptosis. In conclusion, a combination of QU with Sild or PTX ameliorates renal fibrosis by inhibiting ER stress-induced cellular apoptosis through modulation of the GRP75/CHOP/Bax/Bcl2 and oxidative stress pathways.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactational exposure to polystyrene nanoplastics induces oxidative stress, testicular histological alterations, and impaired sperm quality in rat offspring.","authors":"Saeid Fathollahi, Hamid Reza Moradi, Zabihollah Khaksar, Mohammad-Reza Divar, Sajjad Abbasi","doi":"10.1007/s00418-026-02539-w","DOIUrl":"10.1007/s00418-026-02539-w","url":null,"abstract":"<p><p>The widespread presence of nanoplastics in the environment has raised concerns regarding their potential adverse effects on reproductive health, particularly during the early developmental stages. Among these contaminants, polystyrene nanoplastics (PSNPs) can cross biological barriers and accumulate in tissues; however, the reproductive consequences of lactational exposure remain insufficiently understood. This study investigated the effects of maternal exposure to PSNPs during lactation on testicular development, oxidative stress, spermatogenesis, and sperm quality in male rat offspring on postnatal days (PD) 30 and 60. Lactating Sprague Dawley rats were orally administered PSNPs at doses of 0.1, 1, or 10 mg/kg/day from postnatal days 1 to 21. Male offspring were evaluated on PD30 and PD60. Testicular morphometry, histopathological alterations, oxidative stress biomarkers, reproductive hormone levels, sperm characteristics, and immunohistochemical expression of p53 and BCL-2 were also assessed. Histopathological examination revealed degeneration of seminiferous tubules, reduction in germinal epithelium height, and impaired spermatogenic organization, particularly at higher exposure doses. Significant alterations in oxidative stress biomarkers were observed, characterized by an increased total oxidant status and oxidative stress index, accompanied by a reduced antioxidant capacity. Sperm analysis revealed reductions in sperm count, motility, and viability, along with increased morphological abnormalities in the exposed groups. Hormonal evaluation indicated disturbances in serum testosterone, luteinizing hormone, and follicle-stimulating hormone (FSH) levels. Immunohistochemical analyses further demonstrated increased p53 expression and reduced BCL-2 immunoreactivity, suggesting the activation of apoptosis-related pathways. Lactational exposure to PSNPs adversely affects testicular development and sperm quality in male offspring, potentially through oxidative stress and apoptosis-related mechanisms. These findings suggest that early life exposure to nanoplastics during critical developmental periods may contribute to reproductive dysfunction, highlighting the need for further investigation into the long-term biological effects of environmental nanoplastic exposure.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dnmt3b and Dnmt3l knockdown reduces blastocyst development in early mouse embryos.","authors":"Nazlican Bozdemir, Ozgur Cinar, Tugce Oznacar, Ahmet Cevdet Ceylan, Fatma Uysal Cinar","doi":"10.1007/s00418-026-02540-3","DOIUrl":"10.1007/s00418-026-02540-3","url":null,"abstract":"<p><p>A one-cell embryo called a zygote develops into a blastocyst through several successive cell divisions and lineage specification, this process is called early embryo development. Both embryonic genome activation (EGA) and the first lineage specification during early embryonic development depend on tightly coordinated epigenomic organization. Regulation of the epigenome is primarily governed by DNA methylation mediated through DNA methyltransferase (Dnmt) enzymes. Dnmt1 is responsible for the maintenance of methylation during cellular division, while Dnmt3a/Dnmt3b enzymes play a role in the establishment of de novo methylation particularly during gametogenesis and early embryo development. Despite its lack of catalytic activity, Dnmt3l functions as a cofactor enhancing Dnmt3a/3b activity. Dnmt3b deficiency results in global hypomethylation and ultimately embryonic lethality. In this study, we aim to elucidate the effect of Dnmt3b and Dnmt3l silencing on early embryo development. For this purpose, our experimental groups were established using an in vitro mouse embryo development model: control, Dnmt3b small interfering RNA (siRNA), Dnmt3l siRNA, and a nontargeting siRNA group. Following gene silencing at the one-cell stage, embryonic developmental competence, the expression pattern of nonsilenced Dnmt enzymes, global DNA methylation levels, and transcriptome profiles were analyzed at the blastocyst stage. Dnmt3b/3l silencing resulted in decreased global DNA methylation and Dnmt1/3a expression, and reduced blastocyst rate. Differentially expressed genes included those involved in X-chromosome inactivation (Xist), transcriptional regulation (Rn7sk), translation (Eef1a1, Eef2), trophoblast development (Hsd3b1), compaction (Gja1), and oxidative phosphorylation (CYTB, COX1, mt-Rnr1). Our findings indicate that siRNA-mediated knockdown of Dnmt3b and Dnmt3l is associated with reduced blastocyst development, impaired embryo quality, and alterations in DNA methylation-related processes during early embryonic development.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of alveolar epithelial junctions in early lung injury and COVID-19-induced fibrosis.","authors":"Julián Wiegner, Michael Kasper, Mirko H H Schmidt, Kathrin Barth","doi":"10.1007/s00418-026-02533-2","DOIUrl":"10.1007/s00418-026-02533-2","url":null,"abstract":"<p><p>Pulmonary fibrosis is a chronic progressive disease, caused by numerous factors, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Damage to the alveolar epithelial barrier (formed by junctions between alveolar epithelial cells I) has been described as a key mechanism of early fibrosis and therefore could be crucial for COVID-19-associated sequelae. The integrity of adherens junctions is regulated by p120 catenin and is crucial for barrier regulation in epithelial-mesenchymal-transition-driven diseases such as fibrogenesis and cancer. Abundance and expression of p120 catenin and intercellular contact regulating proteins (caveolin-1, P2X7R) were investigated retrospectively in COVID-19 lungs (acute, chronic) compared with healthy controls and interstitial lung disease of different etiologies (n = 6). p120 Catenin was further investigated in early injury models using profibrotic agents in murine lung and human alveolar epithelial cell culture. p120 Catenin abundance was higher in chronic COVID-19 compared with acute COVID-19, suggesting a role in fibrotic development. The interacting proteins caveolin-1 and P2X7R were simultaneously decreased in COVID-19, indicating a role in early pathophysiology. Early epithelial damage showed no changes in p120 catenin and its phospho-Y228 site in cell culture whereas p120 catenin was reduced in murine lung culture. Thus, alterations in and interactions between p120 catenin and caveolae associated proteins may represent a potential mechanism underlying COVID-19-induced pulmonary fibrosis.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential impact of bisphenol S on human arterial endothelial cells from healthy and type-2 diabetic donors: a high-content imaging study.","authors":"Andrea di Credico, Giulia Gaggi, Sandra Bibbò, Marco Marchisio, Angela di Baldassarre, Barbara Ghinassi","doi":"10.1007/s00418-026-02535-0","DOIUrl":"10.1007/s00418-026-02535-0","url":null,"abstract":"<p><p>Endothelial dysfunction is a central mechanism linking type 2 diabetes (T2D) to cardiovascular complications, and environmental endocrine-disrupting chemicals may further perturb vascular homeostasis. Bisphenol S (BPS), widely used as a bisphenol A substitute, is increasingly detected in human and environmental samples, but its impact on endothelial morphology in the context of pre-existing metabolic disease remains poorly defined. Here, we used high-content imaging and Cell Painting to determine whether exposure to 0.1 µM BPS for 96 h induces distinct morphology-based responses in primary human arterial endothelial cells from healthy and T2D donors. Multiplex staining of DNA, RNA-rich regions, RER, Golgi/membrane structures, and mitochondria was combined with automated segmentation, multidimensional feature extraction, sparse partial least-squares discriminant analysis, and inferential statistics. Metabolic status was the main determinant of the endothelial morphology-based profile, clearly separating healthy and T2D-derived cells. In addition, BPS induced a pronounced multidimensional phenotypic shift in healthy endothelial cells, involving nuclear, mitochondrial, RNA-associated, and membrane/perinuclear descriptors. In contrast, T2D-derived cells retained a dominant disease-associated profile, with a less evident whole-cell response to BPS. However, selected RER-associated descriptors remained BPS-responsive, indicating that BPS can still modulate stress-related subcellular organization under diabetic conditions. These findings show that BPS perturbs endothelial morphology under exposure-relevant low-dose conditions but that baseline metabolic status strongly shapes the magnitude and compartmental distribution of this response. The study identifies the diabetic endothelial phenotype as a key modifier of BPS-induced cellular remodeling and supports Cell Painting as a sensitive strategy to resolve context-dependent endothelial responses to environmental pollutants.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences related to sex in adolescent obese Zucker rats: locomotor activity and dendritic arborization of neurons in layer V of the primary motor cortex.","authors":"Lesly Domínguez-Juárez, Adriana Berenice Silva-Gómez","doi":"10.1007/s00418-026-02537-y","DOIUrl":"10.1007/s00418-026-02537-y","url":null,"abstract":"<p><p>Obesity is a metabolic disorder characterized by the accumulation of excess body fat, which has been linked to skeletal muscle and motor behavior changes. Despite the high prevalence of obesity among children and adolescents in Mexico, it has mostly been studied using adult obese animal models. The objective of the present study was to analyze open-field locomotor activity and dendritic length and dendritic spine density in layer V pyramidal neurons of the primary motor cortex (M1) in adolescent (60-day-old) obese Zucker diabetic fatty (ZDF) rats of both sexes. Long-Evans (LE) rats were used as the control group. Female ZDF rats exhibited increased body weight, Lee index, and abdominal circumference. In contrast, male ZDF rats showed a shorter body length together with increased Lee index and abdominal circumference. However, ZDF rats of both sexes displayed elevated triglyceride and cholesterol levels. In addition, hyperglycemia was observed in male ZDF rats. Female ZDF rats showed decreased exploratory activity. The dendritic length of the basilar arbor of M1 neurons was significantly shorter in female and male ZDF rats, with ZDF males exhibiting a smaller basilar arbor than ZDF females. This last result was also observed in the apical arbor of these neurons. There was also a decrease in basilar and apical dendritic spine density in ZDF rats of both sexes. Our results indicate that female ZDF rats show alterations in exploratory behavior and dendritic arborization, whereas ZDF males are affected in terms of dendritic arborization in M1 neurons, which suggests sex differences in the effects of obesity in adolescent Zucker rats.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empagliflozin mitigates lipopolysaccharide-induced tracheal injury in rats via downregulation of IL-6/JAK/STAT3 signaling pathway and stem cell preservation: histological and molecular study.","authors":"Nahla Reda Sarhan, Sally A Elekhtiar, Rasha Elmowafy, Amira I Shrief","doi":"10.1007/s00418-026-02531-4","DOIUrl":"10.1007/s00418-026-02531-4","url":null,"abstract":"<p><p>Lipopolysaccharide (LPS) is a component of the Gram-negative bacterial cell wall and is considered a potent inflammatory inducer. Empagliflozin (EMPA) is a sodium-glucose co-transporter 2 inhibitor used in treatment of type 2 diabetes mellitus. Interleukin-6/Janus kinase/signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) signaling pathway is essential in driving inflammation, fibrosis, and epithelial-mesenchymal transition (EMT). Tracheal basal stem cells are responsible for epithelial regeneration after injury. This study aimed to investigate the potential protective effects of EMPA against LPS-induced tracheal injury, with emphasis on EMT and tracheal basal stem cells. Sixty adult male rats were allocated into four groups: control; EMPA, which received EMPA (10 mg/kg/day) via oral gavage for 28 days; LPS, which received single intratracheal dose of LPS (5 mg/kg) on day 1; and LPS + EMPA, which received single LPS dose and EMPA for 28 days. Tracheal specimens were processed for biochemical, histological, immunohistochemical and RT-quantitative real-time PCR analysis. Compared to the LPS group, the LPS + EMPA group showed marked improvement of histological, ultrastructural ,and biochemical alterations including maintenance of epithelial and cilia integrity, decreased lipid peroxidation, stimulated antioxidant enzyme activities, reduced serum inflammatory cytokines, increased percentage area of E-cadherin (an epithelial marker) immunostaining, decreased percentage area of fibrosis, vimentin (a mesenchymal marker), and pro-apoptotic Bax; and enhanced percentage area of cytokeratin 5/6 (CK5/6) (stem cell marker). Moreover, EMPA downregulated the IL-6/JAK/STAT3 pathway involved in EMT. In conclusion, EMPA alleviated LPS-induced tracheal injury through its antioxidant and anti-inflammatory properties, downregulation of IL-6/JAK/STAT3 signaling pathway, and preservation of the tracheal basal stem cells.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated DNA 5-hydroxymethylation promotes chondrocyte differentiation via TET-mediated epigenetic downregulation of hTERT in human mesenchymal stem cells.","authors":"Naeem Ullah, Fazal Jalil, Muhammad Jaseem Khan, Muhammad Umair, Waseem Iqbal, Aamir Ali Khan","doi":"10.1007/s00418-026-02536-z","DOIUrl":"10.1007/s00418-026-02536-z","url":null,"abstract":"<p><p>DNA methylation is considered a well-regulated mechanism involved in cellular differentiation, particularly in the differentiation of mesenchymal stem cells into chondrocytes. TET family proteins potentially regulate demethylation by the oxidative conversion of 5-methylcytosine (5-mC) into hydroxymethyl cytosine (5-hmC) and then into formylcytosine (5-fC) and carboxyl cytosine (5-caC) in a series of reactions. However, the precise role of TET proteins and the impact of 5-hmC dynamics during chondrocyte differentiation remain unclear. This study aimed to investigate the potential association of 5-hydroxymethylation with TET family proteins and human telomerase reverse transcriptase (hTERT) gene expression during the differentiation of human mesenchymal stem cells (hMSCs) into chondrocytes. Methodology involves hMSCs differentiation into chondrocytes over 16 days of culture, with successful differentiation confirmed by Alcian Blue staining and chondrogenic marker gene (ACAN and COL2A1). Gene and protein expressions of TET1, TET2, TET3, and hTERT were analyzed through real-time polymerase chain reaction (RT-PCR) and western blot. Global changes in DNA 5-hmC level quantified using dot blot and enzyme-linked immunosorbent assay (ELISA). Locus-specific changes within the hTERT promoter gene were analyzed through locus-specific PCR. We observed a substantial increase in the expression levels of TET family proteins TET1 and TET2, as well as high global 5-hmC levels during chondrocyte differentiation. However, human telomerase reverse transcriptase (hTERT) expression was reduced both at the messenger RNA (mRNA) and protein levels throughout the differentiation process. Furthermore, epigenetic analysis revealed that elevated 5-hmC enrichment at the hTERT promoter region was strongly associated with the downregulation of hTERT expression. Our findings suggest that 5-hmC may serve as a potential epigenetic biomarker and regulatory element in chondrocyte differentiation, offering new insights into skeletal development and cartilage-related disorders.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lamin subtype expression in Merkel-cell carcinoma: its relation to polyomavirus infection and tumor metastasis.","authors":"Merel Stiekema, Monique Ummelen, Moritz Jesinghaus, Corinna U Keber, Viktoria Wischmann, Ingrid Moll, Jack Cleutjens, Marc A M J van Zandvoort, Jos L V Broers, Frans C S Ramaekers, Roland Moll","doi":"10.1007/s00418-026-02526-1","DOIUrl":"10.1007/s00418-026-02526-1","url":null,"abstract":"<p><p>Merkel-cell carcinoma (MCC) is known for its high metastatic potential. Studies in several tumor types have proposed a role for up- or downregulation of nuclear A- and B-type lamins in facilitating the process of invasion and metastasis, but such studies are lacking for MCC. Therefore, lamin expression levels were examined in 38 tissue samples from 28 patients with MCC using immunohistochemistry. The series comprised primary tumors and different metastases and both Merkel cell polyomavirus (MCPyV) positive and MCPyV-negative cases. This study revealed that primary MCC tumors express variable, but mostly low levels of A-type lamins, while the B-type lamins are overall highly expressed. No obvious differences in lamin expression were observed between the MCPyV-positive and MCPyV-negative cases. A generally higher A-type lamin expression was detected in MCC metastases, although comparison of primary tumors versus metastases from the same patients showed either no change or up- or downregulation of A-type lamins. Normal Merkel cells were found to express both A- and B-type lamins. Conclusively, our data suggest a flexible A-type lamin expression in the process of MCC carcinogenesis and metastasis, which is an important finding regarding the aggressiveness of MCC and in the debate about the cellular origin of MCC.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant membranous localization of cleaved caspase-3 in anaplastic thyroid carcinoma: Implications for cell proliferation and stemness.","authors":"Ayaka Kashimoto, Noa Fujita, Kazuma Ishida, Kazuki Kanayama, Koichiro Komai, Miyoko Higuchi, Mitsuyoshi Hirokawa, Hiroyuki Ohsaki, Shingo Kamoshida","doi":"10.1007/s00418-026-02530-5","DOIUrl":"10.1007/s00418-026-02530-5","url":null,"abstract":"<p><p>Anaplastic thyroid carcinoma (ATC) is among the most aggressive malignancies. Patients with ATC have poor prognoses and require novel therapies. Cleaved caspase-3 (CC3) has pivotal functions in apoptosis and is usually present in the nuclei and cytoplasm of apoptotic cells. We investigated the aberrant membranous localization of CC3 in thyroid carcinoma (TC) and its diagnostic and clinicobiological significance. We examined the expression of nuclear/cytoplasmic CC3 (n/cCC3) and membranous CC3 (mCC3) in 80 primary and one metastatic TC samples. Receiver operating characteristic curve analysis was used to evaluate their diagnostic efficacy for ATC. Multivariate logistic regression analysis was used to identify risk factors for large tumor size. The n/cCC3 and mCC3 indices were significantly greater in ATC than in other types of TC (P < 0.001). Moreover, the area under the curve and sensitivity of mCC3 were greater than those of n/cCC3 for identifying ATC (0.961 versus 0.948 and 95.0% versus 90.0%). A preabsorption test confirmed the specificity of CC3 immunostaining. However, Western blotting indicated that the anti-CC3 antibody crossreacted with an unknown protein with epitopes common to those of CC3. Significant correlations were detected between Ki-67 and n/cCC3 (ρ = 0.536, P < 0.001) and mCC3 (ρ = 0.680, P < 0.001). Multivariate analysis revealed that mCC3 was an independent risk factor for large tumor size. Double immunofluorescence staining demonstrated that mCC3-expressing ATC cells were Ki-67-negative but occasionally SOX2-positive. Our results suggest that mCC3 may have diagnostic value for ATC and that mCC3-expressing ATC cells may be involved in cell proliferation and stemness.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"164 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}